Renal vasodilatory influence of endogenous carbon monoxide in chronically hypoxic rats
Renal vasodilatory influence of endogenous carbon monoxide in chronically hypoxic rats
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DOI：
10.1152/ajpheart.2000.279.6.h2908
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发表时间：
2000-12-01
影响因子：
4.8
通讯作者：
Walker, BR
中科院分区：
文献类型：
--
作者：
O'Donaughy, TL;Walker, BR
慢性缺氧（CH）减弱清醒大鼠对多种激动剂的全身血管收缩。最近的证据表明，同样减少反应的血管收缩剂在主动脉环CH大鼠可能是由于增加内皮血红素加氧酶（HO）的活性和增强生产的血管扩张剂一氧化碳（CO）。因此，我们推测，缺氧诱导的HO活性增加是负责减少血管收缩反应观察清醒CH大鼠。CH（4周，在0.5大气压）和对照组大鼠肾去神经和仪器的测量肾血流量（RBF）和血压。首先，在清醒大鼠中评估分级静脉输注苯肾上腺素（PE）的肾血管收缩反应。CH大鼠表现出显着减少肾血管收缩反应PE相比，持续甚至急性恢复常氧的控制反应。在另外的实验中，CH大鼠表现出增加肾血管阻力和减少RBF响应HO抑制剂锌原卟啉IX（11 μ mol/kg iv），而肾血流动力学不受抑制剂在对照动物。此外，我们证明了更大的HO酶活性在肾组织中的CH大鼠与对照组相比。这些数据表明，增强HO活性有助于紧张性血管舒张的影响，在肾血管的CH大鼠，可能是负责在这些条件下观察到的血管收缩剂激动剂的敏感性降低。
Chronic hypoxia (CH) attenuates systemic vasoconstriction to a variety of agonists in conscious rats. Recent evidence suggests that similarly diminished responses to vasoconstrictors in aortic rings from CH rats may be due to increased endothelial heme oxygenase (HO) activity and enhanced production of the vasodilator carbon monoxide (CO). Thus we hypothesized that a hypoxia-induced increase in HO activity is responsible for decreased vasoconstrictor responsiveness observed in conscious CH rats. CH (4 wk at 0.5 atm) and control rats were renal denervated and instrumented for the measurement of renal blood flow (RBF) and blood pressure. First, renal vasoconstrictor responses to graded intravenous infusion of phenylephrine (PE) were assessed in conscious rats. CH rats demonstrated significantly diminished renal vasoconstrictor responses to PE compared with control responses that persisted even with acute restoration of normoxia. In additional experiments, CH rats exhibited increased renal vascular resistance and decreased RBF in response to the HO inhibitor zinc protoporphyrin IX (11 mu mol/kg iv), whereas renal hemodynamics were unaffected by the inhibitor in control animals. Furthermore, we demonstrated greater HO enzyme activity in renal tissue from CH rats compared with controls. These data suggest that enhanced HO activity contributes a tonic vasodilatory influence in the renal vasculature of CH rats that may be responsible for the diminished sensitivity to vasoconstrictor agonists observed under these conditions.